ESPE Abstracts

Background: In this study we investigated mortality in children with monogenic diabetes.

Methods: Within the Ukrainian Pediatric Diabetes Register (UPDR) the number of children with type 1 diabetes mellitus (DM1) 0-17 y.o. in 2019 was 9860 (1 in 769), with DM2 - 36 (1 in 210,547) with neonatal DM (NDM) - 66 (1 in 115,000), with MODY - 40 cases (1 in 114,844). We used targeted next generation sequencing (tNGS) of all known NDM genes in any child diagnosed in the first 9 months of life and all known MODY genes in those who was diagnosed after 9 months of life.

Results: Among 106 children with monogenic diabetes 8 patients died to date. 7 (87.5%) had NDM. We found 3 patients with autoimmune monogenic diabetes mellitus (ADM) with mutations in AIRE, FOXP3 and LRBA, 2 of whom had NDM (hemizygous FOXP3 p.R347H and homozygous LRBA p.Glu946Ter). 2 children with ADM/NDM died before age 1 year, and the patient with AIRE p.Cys311fs/p.Arg257Ter died at 15 years. He was admitted to ECU with hypoparathyroidism and died due to severe dyselectrolythemia, ischemic stroke and myocardial infarction. The patients with FOXP3 and LRBA died due to respiratory insufficiency and intestinal gangrene respectively. In both NDM cases results of genetic testing were obtained after death. The patient with a homozygous IPF1 c.1A>G mutation, was diagnosed with NDM at the age of 6 days and died at 6 months due to cytolysis syndrome, cholestatic hepatitis, sepsis and systemic multiple organ failure. 2 NDM patients with EIF2AK3 (p.D164fs/p.E421fs and homozygous p.G1010V) died at an early age. The patient with EIF2AK3 p.D164fs/p.E421fs was diagnosed with diabetes at the age of 13 weeks and died at 3 months due to cerebral edema. The patient with EIF2AK3 p.G1010V had multiple inpatient admissions due to cytolysis syndrome and died at age 2y 2 months due to systemic multiple organ failure. 2 siblings with NDM and ABCC8 p.I49F died at the age 5 and 9 y.o., where 5 y.o. girl died because of pneumonia (had also severe rickets and curvature of the chest) and her 9 y.o. brother died within 1 day after admission to the ECU because of hypertermia, cytolysis syndrome and systemic multiple organ failure.

Conclusions: Whilst ADM and EIF2AK3 are described as a well known cause of death in patients with monogenic diabetes, the cause of death in patients with IPF1 and ABCC8 has not yet been widely described.